Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The role of protein kinase C in cell surface signal transduction and tumour promotion

Nature volume 308, pages 693–698 (1984)Cite this article

Abstract

Protein kinase C has a crucial role in signal transduction for a variety of biologically active substances which activate cellular functions and proliferation. When cells are stimulated, protein kinase C is transiently activated by diacylglycerol which is produced in the membrane during the signal-induced turnover of inositol phospholipids. Tumour-promoting phorbol esters, when intercalated into the cell membrane, may substitute for diacylglycerol and permanently activate protein kinase C. The enzyme probably serves as a receptor for the tumour promoters. Further exploration of the roles of this enzyme may provide clues for understanding the mechanism of cell growth and differentiation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Inoue, M., Kishimoto, A., Takai, Y. & Nishizuka, Y. J. biol. Chem. 252, 7610–7616 (1977).

    CAS  PubMed  Google Scholar 

  2. Takai, Y. et al. J. biol. Chem. 254, 3692–3695 (1979).

    CAS  PubMed  Google Scholar 

  3. Takai, Y., Kishimoto, A., Kikkawa, U., Mori, T. & Nishizuka, Y. Biochem. biophys. Res. Commun. 91, 1218–1224 (1979).

    Article  CAS  PubMed  Google Scholar 

  4. Kishimoto, A., Takai, Y., Mori, T., Kikkawa, U. & Nishizuka, Y. J. biol. Chem. 255, 2273–2276 (1980).

    CAS  PubMed  Google Scholar 

  5. Nishizuka, Y. Molec. Biol. Biochem. Biophys. 32, 113–135 (1980).

    Article  CAS  Google Scholar 

  6. Nishizuka, Y. Phil. Trans. R. Soc. B. 302, 101–112 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Nishizuka, Y. & Takai, Y. Cold Spring Harb. Conf. Cell Proliferation 8, 237–249 (1981).

    CAS  Google Scholar 

  8. Nishizuka, Y. Trends biochem. Sci. 8, 13–16 (1983).

    Article  CAS  Google Scholar 

  9. Takai, Y., Kishimoto, A. & Nishizuka, Y. in Calcium and Cell Function Vol. 2 (ed. Cheung, W. Y.) 385–412 (Academic, New York, 1982).

    Book  Google Scholar 

  10. Takai, Y., Kikkawa, U., Kaibuchi, K. & Nishizuka, Y. Adv. Cyclic Nucleotide Res. (in the press).

  11. Nishizuka, Y., Takai, Y., Kishimoto, A., Kikkawa, U. & Kaibuchi, K. Recent Prog. Horm. Res. 40, 301–345 (1984).

    CAS  PubMed  Google Scholar 

  12. Kaibuchi, K., Takai, Y. & Nishizuka, Y. J. biol. Chem. 256, 7146–7149 (1981).

    CAS  PubMed  Google Scholar 

  13. Mori, T., Takai, Y., Minakuchi, R., Yu, B. & Nishizuka, Y. J. biol. Chem. 255, 8378–8380 (1980).

    CAS  PubMed  Google Scholar 

  14. Wise, B. C. et al. J. biol. Chem. 257, 8489–8495 (1982).

    CAS  PubMed  Google Scholar 

  15. Kuo, J. F. et al. Proc. natn. Acad. Sci. U.S.A. 77, 7039–7043 (1980).

    Article  ADS  CAS  Google Scholar 

  16. Kikkawa, U., Takai, Y., Minakuchi, R., Inohara, S. & Nishizuka, Y. J. biol. Chem. 257, 13341–13348 (1982).

    CAS  PubMed  Google Scholar 

  17. Kishimoto, A., Kajikawa, N., Shiota, M. & Nishizuka, Y. J. biol. Chem. 258, 1156–1164 (1983).

    CAS  PubMed  Google Scholar 

  18. Nimmo, H. G. & Cohen, P. Adv. Cyclic Nucleotide Res. 8, 145–266 (1977).

    CAS  PubMed  Google Scholar 

  19. Krebs, E. G. & Beavo, J. A. A. Rev. Biochem. 48, 923–959 (1979).

    Article  CAS  Google Scholar 

  20. Michell, R. H. Biochim. biophys. Acta 415, 81–147 (1975).

    Article  CAS  PubMed  Google Scholar 

  21. Berridge, M. J. Molec. cell. Endocr. 24, 115–140 (1981).

    Article  CAS  PubMed  Google Scholar 

  22. Michell, R. H., Kirk, C. J., Jones, L. M., Downes, D. P. & Creba, J. A. Phil. Trans. R. Soc. B296, 123–137 (1981).

    CAS  Google Scholar 

  23. Hokin, M. R. & Hokin, L. E. J. biol. Chem. 203, 967–977 (1953).

    CAS  PubMed  Google Scholar 

  24. Downes, P. & Michell, R. H. Cell Calcium 3, 467–502 (1982).

    Article  CAS  PubMed  Google Scholar 

  25. Berridge, M. J., Dawson, R. M. C., Downes, C. P., Heslop, J. P. & Irvine, R. F. Biochem. J. 212, 473–482 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Abdel-Latif, A. A., Akhtar, R. A. & Hawthorne, J. N. Biochem. J. 162, 61–73 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kawahara, Y., Takai, Y., Minakuchi, R., Sano, K. & Nishizuka, Y. Biochem. biophys. Res. Commun. 97, 309–317 (1980).

    Article  CAS  PubMed  Google Scholar 

  28. Sano, K., Takai, Y., Yamanishi, J. & Nishizuka, Y. J. biol. Chem. 258, 2010–2013 (1983).

    CAS  PubMed  Google Scholar 

  29. Lyons, R. M., Stanford, N. & Majerus, P. W. J. clin. Invest. 56, 924–936 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Haslam, R. J. & Lynham, J. A. Biochem. biophys. Res. Commun. 77, 714–722 (1977).

    Article  CAS  PubMed  Google Scholar 

  31. Leyasu, H., Takai, Y., Kaibuchi, K., Sawamura, M. & Nishizuka, Y. Biochem. biophys. Res. Commun. 108, 1701–1708 (1982).

    Article  Google Scholar 

  32. Yagi, K., Yazawa, M., Kakiuchi, S., Ohshima, M. & Uenishi, K. J. biol. Chem. 253, 1338–1340 (1978).

    CAS  PubMed  Google Scholar 

  33. Imaoka, T., Lynham, J. A. & Haslam, R. J. J. biol. Chem. 258, 11404–11414 (1983).

    CAS  PubMed  Google Scholar 

  34. Rittenhouse-Simmons, S. J. clin. Invest. 63, 580–587 (1979).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bell, R. L. & Majerus, P. W. J. biol. Chem. 255, 1790–1792 (1980).

    CAS  PubMed  Google Scholar 

  36. Kaibuchi, K., Sano, K., Hoshijima, M., Takai, Y. & Nishizuka, Y. Cell Calcium 3, 323–335 (1982).

    Article  CAS  PubMed  Google Scholar 

  37. Kaibuchi, K. et al. J. biol. Chem. 258, 6701–6704 (1983).

    CAS  PubMed  Google Scholar 

  38. Hecker, E. Meth. Cancer Res. 6, 439–484 (1971).

    CAS  Google Scholar 

  39. Weinstein, I. B., Lee, L. S., Mufson, A. & Yamasaki, H. J. supramolec. Struct. 12, 195–208 (1979).

    Article  CAS  Google Scholar 

  40. Blumberg, P. M. CRC Crit. Rev. Tox. 8, 153–197 (1980).

    Article  CAS  Google Scholar 

  41. Castagna, M. et al. J. biol. Chem. 257, 7847–7851 (1982).

    CAS  PubMed  Google Scholar 

  42. Yamanishi, J. et al. Biochem. biophys. Res. Commun. 112, 778–786 (1983).

    Article  CAS  PubMed  Google Scholar 

  43. Kikkawa, U., Takai, Y., Tanaka, Y., Miyake, R. & Nishizuka, Y. J. biol. Chem. 258, 11442–11445 (1983).

    CAS  PubMed  Google Scholar 

  44. Dunphy, W. G., Kochenburger, R. J., Castagna, M. & Blumberg, P. M. Cancer Res. 41, 2640–2647 (1981).

    CAS  PubMed  Google Scholar 

  45. Horowitz, A. D., Greenebaum, E. & Weinstein, I. B. Proc. natn. Acad. Sci. U.S.A. 78, 2315–2319 (1981).

    Article  ADS  CAS  Google Scholar 

  46. Solanki, V. & Slaga, T. J. Proc. natn. Acad. Sci. U.S.A. 78, 2549–2553 (1981).

    Article  ADS  CAS  Google Scholar 

  47. Ashendel, C. L., Staller, J. M. & Boutwell, R. K. Biochem. biophys. Res. Commun. 111, 340–345 (1983).

    Article  CAS  PubMed  Google Scholar 

  48. Sando, J. J. & Young, M. C. Proc. natn. Acad. Sci. U.S.A. 80, 2642–2646 (1983).

    Article  ADS  CAS  Google Scholar 

  49. Leach, K. L., James, M. L. & Blumberg, P. M. Proc. natn. Acad. Sci. U.S.A. 80, 4208–4212 (1983).

    Article  ADS  CAS  Google Scholar 

  50. Shoyab, M. & Boaze, R. Jr. Cold Spring Harb. Conf. Cell. Proliferation 11 (in the press).

  51. Delclos, K. B., Yeh, E. & Blumberg, P. M. Proc. natn. Acad. Sci. U.S.A. 80, 3054–3058 (1983).

    Article  ADS  CAS  Google Scholar 

  52. Kraft, A. S., Anderson, W.B., Cooper, H. L. & Sando, J. J. J. biol. Chem. 257, 13193–13196 (1982).

    CAS  PubMed  Google Scholar 

  53. Shoyab, M. & Todaro, G. J. Nature 388, 451–455 (1980).

    Article  ADS  Google Scholar 

  54. Niedel, J. E., Kuhn, L. J. & Vandenbark, G. R. Proc. natn. Acad. Sci. U.S.A. 80, 36–40 (1983).

    Article  ADS  CAS  Google Scholar 

  55. Kikkawa, U., Miyake, R., Tanaka, Y., Takai, Y. & Nishizuka, Y. Cold Spring Harb. Conf. Cell Proliferation 11, (in the press).

  56. Fujiki, H. et al. in Cellular Interactions by Environmental Tumor Promoters (ed. Sugimura, T.) (Japan Sci. Soc., Tokyo, in the press).

  57. Swilen, A. M. F., Hawthorne, J. N. & Azia, N. Biochem, Pharmac. 32 (in the press).

  58. Kajikawa, N. et al. Biochem. biophys. Res. Commun. 116, 743–750 (1983).

    Article  CAS  PubMed  Google Scholar 

  59. Witz, G., Goldstein, B. D., Amoruso, M., Stone, D. S. & Troll, W. Biochem. biophys. Res. Commun. 97, 883–888 (1980).

    Article  CAS  PubMed  Google Scholar 

  60. Rink, T. J., Sanchez, A. & Hallam, T. J. Nature 305, 317–319 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  61. Knight, D. E., Hallam, T. J. & Scrutton, M. C. Nature 296, 256–257 (1982).

    Article  ADS  CAS  PubMed  Google Scholar 

  62. Kaibuchi, K., Sawamura, M., Kikkawa, U., Takai, Y. & Nishizuka, Y. in Inositol and Phosphoinositides (eds Bleasdale, J. E., Eichberg, J. & Hauser, J.) (Humana, Dallas, in the press).

  63. Knight, D. E. & Baker, P. F. FEBS Lett. 160, 98–100 (1983).

    Article  CAS  PubMed  Google Scholar 

  64. Kojima, I., Lippes, H., Kojima, K. & Rasmussen, H. Biochem. biophys. Res. Commun. 116, 555–562 (1983).

    Article  CAS  PubMed  Google Scholar 

  65. Zawalich, W., Brown, C. & Rasmussen, H. Biochem. biophys. Res. Commun. 117, 448–455 (1983).

    Article  CAS  PubMed  Google Scholar 

  66. Garrison, J. C., Johnsen, D. E. & Campanile, C. P. J. biol. Chem. (in the press).

  67. Fain, J. N., Li, S.-Y., Litosch, I. & Wallace, M. Biochem. biophys. Res. Commun. (in the press).

  68. Mastro, A. M. & Smith, M. C. J. cell. Physiol. 116, 51–56 (1983).

    Article  CAS  PubMed  Google Scholar 

  69. Werth, D. K., Niedel, J. E. & Pastan, I. J. biol Chem. 258, 11423–11426 (1983).

    CAS  PubMed  Google Scholar 

  70. Le Peuch, C. J., Ballester, R. & Rosen, O. M. Proc. natn. Acad. Sci. U.S.A. 80, 6858–6862 (1983).

    Article  ADS  CAS  Google Scholar 

  71. Naka, M., Nishikawa, M., Adelstein, R. S. & Hidaka, H. Nature 306, 490–492 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  72. Schatzman, R. C., Grifo, J. A., Merrick, W. C. & Kuo, J. F. FEBS Lett. 159, 167–170 (1983).

    Article  CAS  PubMed  Google Scholar 

  73. Martin, G. S. & Gilmore, T. Nature 306, 487–490 (1983).

    Article  ADS  PubMed  Google Scholar 

  74. Streb, H., Irvine, R. F., Berridge, M. J. & Schulz, I. Nature 306, 67–69 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  75. Bell, R. L., Kennerley, D. A., Stanford, N. & Majerus, P. W. Proc. natn. Acad. Sci. U.S.A. 76, 3238–3241 (1979).

    Article  ADS  CAS  Google Scholar 

  76. Billah, M. M., Lapetina, E. G. & Cuatrecasas, P. J. biol. Chem. 256, 5399–5403 (1981).

    CAS  PubMed  Google Scholar 

  77. Graff, G., Stephenson, J. H., Glass, D. B., Haddox, M. K. & Goldberg, N. D. J. biol. Chem. 253, 7662–7676 (1978).

    CAS  PubMed  Google Scholar 

  78. Takai, Y., Kaibuchi, K., Matsubara, T. & Nishizuka, Y. Biochem. biophys. Res. Commun. 101, 61–67 (1981).

    Article  CAS  PubMed  Google Scholar 

  79. Haslam, R. J., Salama, S. E., Fox, J. E. B., Lynham, J. A. & Davidson, M. M. L. in Platelets: Cellular Response Mechanisms and their Biological Significance (eds Rotman, A., Meyer, F. A., Gitler, C. & Silderberg, A.) 213–231 (Wiley, New York, 1980).

    Google Scholar 

  80. Schultz, K. D., Schultz, K. & Schultz, G. Nature 265, 750–751 (1977).

    Article  ADS  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Kobe University School of Medicine, Kobe, 650, Japan

    Yasutomi Nishizuka

  2. Department of Cell Biology, National Institute for Basic Biology, Okazaki, 444, Japan

    Yasutomi Nishizuka

Authors
  1. Yasutomi Nishizuka
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nishizuka, Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308, 693–698 (1984). https://doi.org/10.1038/308693a0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/308693a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing